A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union-sourced Herceptin.

PURPOSE: This first-in-human study of HD201 was designed to evaluate the pharmacokinetic (PK) equivalence between this biosimilar candidate and trastuzumab sourced in the European Union (EU-trastuzumab)*. METHODS: In this randomized, blinded, single-dose comparative PK study, healthy male subjects were randomized to receive a single 6 mg/kg IV dose of HD201 or EU-trastuzumab. The primary PK end point was AUC0-∞. Equivalence was determined by using the predefined margins of 0.8 to 1.25. Other PK parameters were included as secondary end points. FINDINGS: Baseline demographic characteristics for the 73 randomized subjects were similar across the 2 groups: median age 29 and 30 years old (ranges 19 - 45), median weight 78.6 and 81.7 kg (ranges 60.2 - 101). The 90% CIs for the geometric least squares mean of the AUC0-∞ were included within the margins of 0.8 to 1.25. All other PK parameters were comparable for both HD201 and EU-trastuzumab. The proportions of subjects who experienced adverse events related to the study drug were 61.8% and 82.9% in the HD201 and EU-trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug were infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose. IMPLICATIONS: This study reported the PK equivalence between HD201 and EU-trastuzumab. HD201 was well tolerated with no safety concerns after single-dose administration in healthy male subjects. EudraCT No.: 2012-000805-56.

Core competencies for pharmaceutical physicians and drug development scientists.

Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

Accuracy of a Novel Non-Invasive technology based EZSCAN system for the diagnosis of diabetes mellitus in Chinese.

BACKGROUND: A new simple technique based on iontophoresis technology (EZSCAN, Impeto Medical, Paris, France) has recently been developed for the screening of diabetes. In the present study, we investigated the accuracy of this system for the diagnosis of diabetes mellitus in Chinese. METHODS: We performed the EZSCAN test in diabetic and non-diabetic subjects. EZSCAN measures electrochemical conductance (EC) at forehead, hands and feet, and derives a diabetes index with a value ranging from 0 to 100. Diabetes mellitus was defined as a plasma glucose concentration of at least 7 mmol/l at fasting or 11.1 mmol/l at 2 hours after glucose load, or as the use of antidiabetic drugs. RESULTS: The 195 study participants (51% men, mean age 52 years) included 75 diabetic patients (use of antidiabetic drugs 81%) and 120 non-diabetic subjects. EC (micro Siemens, µSi) was significantly (P < 0.001) lower in diabetic patients at the hands (44 vs. 61) and feet (51 vs. 69) locations, but not at the forehead (15 vs. 17, P = 0.39). When a diabetes index of 40 (suggested by the manufacturer) was used as the threshold, the sensitivity and specificity for the diagnosis of diabetes mellitus was 85% and 64%, respectively. In 80 patients who underwent an oral glucose tolerance test, EC at hands and feet and the diabetes index were significantly (P < 0.001) associated with both 2-hour post-load plasma glucose and serum glycosylated haemoglobin. CONCLUSIONS: EZSCAN might be useful in screening diabetes mellitus with reasonable sensitivity and specificity.

A new tool to detect kidney disease in Chinese type 2 diabetes patients: comparison of EZSCAN with standard screening methods.

BACKGROUND: EZSCAN(®) (Impeto Medical, Paris, France), a noninvasive device that assesses sweat gland dysfunction using reverse iontophoresis, also detects early dysglycemia. Given the interrelationships among dysglycemia, vasculopathy, and neuropathy, EZSCAN may detect kidney disease in diabetes (DKD). METHODS: An EZSCAN score (0-100) was calculated using a proprietary algorithm based on the chronoamperometry analysis. We measured the score in 50 Chinese type 2 diabetes patients without DKD (urinary albumin-creatinine ratio [ACR] <2.5 mg/mmol in men or ACR <3.5 mg/mmol in women and estimated glomerular filtration rate [eGFR] >90 mL/min/1.73 m(2)) and 50 with DKD (ACR ≥25 mg/mmol and eGFR <60 mL/min/1.73 m(2)). We used spline analysis to determine the threshold value of the score in detecting DKD and its sensitivity and specificity. RESULTS: EZSCAN scores were highly correlated with log values of eGFR (r=0.67, P<0.0001) and ACR (r=-0.66, P<0.0001). Using a cutoff value of 55, the score had 94% sensitivity, 78% specificity, and a likelihood ratio of 4.2 to detect DKD with a positive predictive value of 81% and a negative predictive value of 93%. On multivariable analysis, DKD was independently associated with EZSCAN score (ß=-0.72, P=0.02), smoking status (1=never, 0=current/former) (ß=-2.37, P=0.02), retinopathy (1=yes, 0=no) (ß=3.019, P=0.01), triglycerides (ß=2.56, P=0.013), and blood hemoglobin (ß=-0.613, P=0.04). Patients without DKD but low EZSCAN score (n=10) had longer duration of disease (median [interquartile range], 13 [9-17] vs. 8 [4-16] years; P=0.017) and were more likely to have retinopathy (36.7% vs. 5.1%, P=0.02), lower eGFR (98 [95.00-103] vs. 106 [98.5-115], P=0.036), and treatment with renin-angiotensin system blockers (81.8% vs. 25.6%, P=0.002) than those with a normal score. CONCLUSION: EZSCAN may detect high-risk subjects for DKD in Chinese populations.

A new non-invasive technology to screen for dysglycaemia including diabetes.

OBJECTIVE: Assess the ability of a new device based on electrochemical principles using iontophoresis (the EZSCAN) to detect impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). METHODS: Eligible Asian Indian subjects, n=212, had anthropometric and blood pressure measurements, followed by an OGTT, HbA1c, serum lipids tests and EZSCAN measurement. RESULTS: Biochemically, 24 subjects were diagnosed with DM, 30 with IGT, 57 subjects had normal glucose tolerance (NGT) with metabolic syndrome (MS) and 101 had NGT without MS. Fasting plasma glucose (FPG) and HbA1c levels were highest in the DM group (p<0.0001 for both). HDL-C levels were different (p=0.015). FPG at a cut-off level of 7.0 mmol/L had a low sensitivity to detect DM (29%) EZSCAN had a 75% sensitivity to detect DM, 70% for IGT and 84% for NGT with MS at threshold >50%. CONCLUSIONS: FPG had low sensitivity to detect DM in the study group. EZSCAN demonstrated good sensitivity to detect IGT and DM and also identified NGT with MS. The concept of measuring ion fluxes through the skin appears to be a powerful method for early detection of MS, IGT and DM.